[What to do when faced with hyperprolactinemia?]. / Que faire devant une hyperprolactinémie?

Hyperprolactinemia causes a certain number of clinical syndromes whose sequels vary much depending on the age group. It is a common affection as frequent in women as in males and it necessitates prolonged treatment. It may have several causes, the most frequent ones are: adverse drug reactions, prolactinomas, disturbed distribution of dopamine and hyperthyroidism. Evaluation includes repeated measurements of prolactin, T4, and TSH, a radiologic work-up including a CT-scan or magnetic resonance imaging. In the case of a prolactinoma the choice of treatment depends on size and evolution of the adenoma. Bromocriptine permits to correct hyperprolactinemia in the majority of cases. After adequate treatment of pituitary adenoma these are no contraindications for pregnancy, once fertility has returned.

[Hypercalcemia in Addison's disease caused by bilateral adrenal hemorrhage]. / Hypercalcémie lors d'une maladie d'Addison sur hémorragie surrénalienne bilatérale.

The case is reported of a 36-year-old woman presenting with progressive hypercalcemia which led to the diagnosis of adrenocortical insufficiency of recent origin. Adrenal failure developed soon after septic shocks in this heparin anticoagulated patient post leg amputation for Buerger's disease. The clinical, biological and radiological (CT scan) data are consistent with bilateral adrenal hemorrhage as the cause of primary adrenal insufficiency. The pathogenesis of hypercalcemia in this condition is discussed.

Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia.

Since hypothermia is commonly used to lower local and general metabolism during cardiopulmonary bypass, we attempted to identify its specific effects on glucose-insulin interactions. A group of nondiabetic patients undergoing hypothermic (28 degrees C) cardiopulmonary bypass with ischemic (cold) cardiac arrest was compared to a similar group operated on under normothermic conditions with potassium cardioplegia. In the absence of exogenous dextrose administration, hypothermia blocked insulin secretion for the duration of the operation. It also inhibited insulin secretion in response to an exogenous dextrose load (e.g., the priming fluid of the cardiopulmonary bypass circuit) or a glucagon injection, but this inhibition was lifted by rewarming. Blood glucose levels, which during normothermia were mildly elevated even in the absence of dextrose administration, remained normal during the hypothermic phase of cardiopulmonary bypass. By the end of the rewarming period, however, blood glucose levels had reached the same level as observed under normothermic bypass, a fact suggesting that the cold inhibition of hepatic glucose production had been only temporary. Cold inhibition of hepatic glucose production also explains why glucose clearance after a sudden dextrose load was initially faster at low body temperature than at normal temperature. Glucose-clamp studies indicated that insulin resistance was initiated by anesthesia and surgical trauma, and further accentuated by cardiopulmonary bypass, in association with elevated levels of hormones indicative of surgical stress. Regardless of body temperature changes, the assimilation of glucose by nondiabetic subjects during and immediately after bypass called for the infusion of large doses of insulin. A comparison with diabetic subjects showed that insulin-dependent patients (type I diabetes) required no more insulin during cardiopulmonary bypass than normal subjects, whereas patients with type II diabetes exhibited a marked insulin resistance during the operation and in the immediate postoperative period.

Sulfonylureas in insulin-dependent (type I) diabetes: evidence for an extrapancreatic effect in vivo.

The effect of glibenclamide treatment on insulin-mediated glucose disposal was studied in eight C-peptide-negative type I diabetic patients. The patients were studied twice by the euglycemic insulin clamp technique. One of the two experiments was preceded by glibenclamide treatment at the dose of 5 mg, three times daily for 15 days; half of the patients had the first test before and the second test after sulfonylurea treatment, and vice versa. Insulin was infused for four periods of 2 h each sequentially at 0.5, 1.0, 2.0, and 5.0 mU kg-1 min-1; for each insulin infusion period, the steady state plasma free insulin levels were comparable with or without glibenclamide. The mean +/- SEM plasma glucose concentration was 88 +/- 2 mg/dl in both experiments. The insulin-mediated glucose disposal rate was greater with glibenclamide during the first insulin infusion period (which generated plasma free insulin levels within the physiological range) 2.68 +/- 0.32 mg kg-1 min-1 with glibenclamide vs. 1.97 +/- 0.20 mg kg-1 min-1 without glibenclamide (P less than 0.005). However, glucose disposal rates did not differ in the diabetic patients with or without glibenclamide treatment during the second, third, and fourth insulin infusion periods, which generated plasma free insulin levels in the supraphysiological range. These results provide evidence for an extrapancreatic effect of glibenclamide at low insulin concentrations during euglycemic clamping in patients with insulin-dependent diabetes mellitus. However, this effect was not reflected clinically in either an increased rate of hypoglycemic reactions or decreased insulin needs during the short term period of treatment.

Alterations of insulin and glucose metabolism during cardiopulmonary bypass under normothermia.

Anesthesia, surgical trauma, heparinization, priming volume composition, and temperature control of the heart-lung machine individually affect carbohydrate, protein, or lipid metabolism during cardiac operations. The impact of some of these factors on glucose and insulin regulation was assessed before, during, and after normothermic cardiopulmonary bypass in nondiabetic patients with use of a servo-controlled insulin delivery system. With a glucose-free prime, cardiopulmonary bypass induced a slight hyperglycemia but no endogenous insulin response, suggesting a partial inhibition of insulin secretion. Nonetheless, insulin release could be stimulated by exogenous glucagon. A glucose load in the priming fluid led to marked and persistent hyperglycemia without commensurate insulin release. Elevated stress hormone levels, a concomitant reduction of insulin release and insulin action, and a depression of peripheral glucose utilization, as demonstrated by glucose clamp experiments, contributed to these perturbations of glucose and insulin metabolism. Although the metabolic alterations observed are not critical in routine cardiac operations, they may become clinically significant in postoperative states with unusual persistence of stress conditions.

Insulin resistance in Type 1 (insulin-dependent) diabetes: dependence on plasma insulin concentration.

Sensitivity to insulin in vivo was studied in six Type 1 diabetic patients without residual insulin secretion and without clinical insulin resistance, and in eight non-diabetic subjects, using the euglycaemic insulin clamp technique. Insulin was infused for four periods of 2 h sequentially at 0.5, 1.0, 2.0 and 5.0 mU X kg-1 X min-1; for each insulin infusion period the steady-state plasma free insulin levels were comparable in the diabetic and non-diabetic subjects. The mean +/- SEM plasma glucose concentration was 4.9 +/- 0.03 mmol/l in the diabetic subjects (coefficient of variation of plasma glucose values: 5.7 +/- 0.7%) and 4.6 +/- 0.01 mmol/l in the control subjects (coefficient of variation: 5.1 +/- 0.6%). Insulin-mediated glucose disposal was lower in the diabetic than in the non-diabetic subjects at the two lower insulin infusion rates (mean +/- SEM = 2.03 +/- 0.27 versus 4.8 +/- 0.64 mg X kg-1 X min-1 at the first insulin infusion rate, p less than 0.01, and 5.59 +/- 0.59 versus 8.36 +/- 0.61 mg X kg-1 X min-1 at the second insulin infusion rate, p less than 0.01). However, insulin-induced glucose uptake did not differ significantly between the two groups at the third and fourth rates of insulin infusion. These results show that impaired insulin sensitivity in Type 1 diabetes is dependent on insulin concentration.

[Sensitivity to insulin in type I diabetes. Preliminary report]. / Sensibilité à l'insuline dans le diabète de type I. Rapport préliminaire.

In vivo sensitivity to insulin was assessed by the euglycaemic insulin clamp technique in 5 type I diabetic subjects without residual insulin secretion and in 5 non-diabetic control subjects. Insulin was infused at increasing rates of 0.5, 1.0, 2.0 and 5.0 mU/kg/min in 4 periods of 2 hours. The diabetic subjects were resistant to insulin during the 1st and 2nd insulin infusion periods corresponding to the rates of 0.5 and 1.0 mU/kg/min, when compared to the non-diabetic subjects. However, glucose disposal rates were similar in the diabetic and control subjects at the 2 higher insulin infusion rates (2.0 and 5.0 mU/kg/min). Thus insulin resistance in type I diabetes is dependent on insulin concentration.